Project Summary/Abstract: Mouse Modeling Mice are by far the most commonly used vertebrate research model organism for biomedical research, and the ability to generate efficiently genetically-engineered mouse models (GEMM), maintain those mice, and use them for sophisticated experimentation is the basis for the dominance of mice for mammalian biomedical research. As with most biomedical research platforms, the utilization of mice is complex, and often researchers need specialized support to accomplish their mouse experiments. The Mouse Modeling (MM) Shared Resource is focused on supporting researchers doing mouse experimentation by offering a broad range of services that are adapted for specific experimental needs, updating services with the latest technological approaches and doing this service in an efficient and cost-effective manner. By keeping the focus on flexibility, cutting-edge capability and efficiency of services, we have been able to support mouse model experimentation by many researchers and remain financially solvent for over 21 years. The vast majority of the experiments we support are cancer-focused, with other major areas including neuroscience, infectious disease and antibody generation. During the current award period services were performed for 27 Cancer Center Members, 25 of whom now are Members of all 4 NCCC Programs (CPS [1], CBT [11], ICI [10], and TEC [3]). NCCC Funded Members represented 37% of Total MM projects served (549), and we are requesting only 24% of the Total MM Operating Budget from CCSG support. As an example of value added to NCCC research, ?Floxed? ID2 mice were generated by the MM Shared Resource for a study investigating the role of ID2 in glioma biology, and now these mice are available for other researchers, here and outside Dartmouth, and can be combined with Cre-expressing mice to study the biology of ID2, a gene that that plays a role in multiple different cancers. In a second study involving genetically engineered mice, including a knock-in of a Cre-expression-regulated allele of constitutively active P110? of P13 kinase, the resulting model was the first reported rapidly developing murine breast tumor model that generates predominantly adenocarcinoma breast tumors, pathologically similar to human breast cancer. In contrast, other models are either very slow to develop or generate sarcomatoid breast tumors, which are rare in human breast cancer. MM?s menu of services constantly is evolving to respond to changing technologies and changing needs of new and established faculty at Dartmouth. Recently, we have been more involved providing mouse model experimentation services to support labs that either are not experienced with mouse experimentation or do not have sufficient lab personnel to support needed mouse studies, such as engineering faculty from Dartmouth?s Thayer School of Engineering, or research clinical faculty from Dartmouth-Hitchcock. Another new area of focus for MM is the use of CRISPR/Cas9 to make directly targeted genetic modifications in mouse zygotes with no intermediate tissue culture step with ES cells. Multiple mouse models have been made, and we continue to develop skills with this powerful technology.